Natural Course of Moderate Cardiac Allograft Rejection (International Society for Heart Transplantation Grade 2) Early and Late After Transplantation

Publisher Website
Google Scholar
Abstract
Background The significance of International Society for Heart Transplantation (ISHT) grade 2 cardiac allograft rejection has been questioned, and the medical community is not in complete agreement as to its clinical management. We therefore retrospectively analyzed the follow-up of all available endomyocardial biopsy samples obtained from 161 transplant patients since introduction of the ISHT nomenclature at our institution. Methods and Results Of 2868 biopsies performed 3 days to 8.9 years after transplantation, 420 biopsies had no follow-up or were preceded by intensified immunosuppression and were excluded from analysis. Of the remaining 2448 biopsies, 374 (15.3%) were repeat biopsies performed 7 to 10 days after prior ISHT 2 rejection without change of treatment. Of these, 70 (18.7%) had progressed to ≥ISHT 3A, whereas 82 (21.9%) remained unchanged and 222 (59.4%) resolved. In contrast, follow-up of 2074 biopsies with lower-grade rejection showed graft rejection classified as ≥ISHT 3A in 153 (7.4%), ISHT 2 in 240 (11.6%), and ≤ISHT 1B in 1681 (81.1%) biopsy samples ( P <.0001). In univariate analysis, the odds ratio (OR) of graft rejection ≥ISHT 3A after ISHT 2 rejection was 2.89. Other univariate predictors of rejection ≥ISHT 3A were time after transplantation (OR=0.96 per month, P <.0001), blood group type B (OR=1.62, P <.005), “Quilty” lesion on previous biopsy (OR=1.70, P <.005), number of HLA mismatches (OR=1.27 per mismatch, P <.005), female sex (OR=1.55, P <.05), and serum creatinine level (OR=0.93 per 10 μmol/L, P <.005). Young age of recipients was a risk factor during long-term (≥2 years) follow-up ( P <.002), and lower cyclosporine level was a risk factor during the first month after transplantation ( P <.01). In multivariate logistic regression analysis, ISHT 2 rejection on previous biopsy remained the strongest predictor of rejection ≥ISHT 3A (OR=2.40, P <.0001). Conclusions Several factors independently increase the risk of rejection classified as ≥ISHT 3A. The strongest predictor of a grade of ≥ISHT 3A was ISHT 2 rejection on the previous biopsy obtained 7 to 10 days earlier. Therefore, ISHT 2 graft rejection is of clinical significance, and short-term follow-up appears to be warranted even late after transplantation.